An understanding of ganglioside metabolism and function at the nerve-ending is one of our long-term objectives. Gangliosides in the synaptic membrane are of special interest since these are believed to play a role in synaptic transmission. We shall study the origin of this fraction to determine whether axonal transport is the primary source, as now appears likely, or whether local synthesis can also contribute. The metabolic fate of individual gangliosides in this membrane will be investigated with the double-label technique, and the rat optic system will be a convenient experimental model for studying the metabolism of those which arrive by axonal transport. The possibility of trans-synaptic migration of gangliosides will also be studied with the double-label technique. Preliminary observation of axonal transport of myelin lipids will be followed up with experiments to distinguish between direct transport to myelin and an indirect mechanism involving first transport to the axolemma followed by lipid exchange between that membrane and myelin. We shall continue our structural analysis of gangliosides and related glycolipids, our emphasis during the next few years being on the peripheral nervous system. This will include oligosaccharide structures as well as lipophilic composition. We plan to follow up our initial findings on myelin gangliosides with a more systematic study of these substances in CNS and PNS myelin, including an inquiry into their possible biological roles in this membrane. Our continuing study of ganglioside alterations in neurological diseases will focus on multiple sclerosis and other putative slow virus conditions. BIBLIOGRAPHIC REFERENCES: Gangliosides of peripheral nerve myelin. J.W. Fong, R.W. Ledeen, S.K. Kundu and S.W. Brostoff (1976). J. Neurochem. 26, 157. Gangliosides of the neuron: localization and origin. R.W. Ledeen, J.A. Skrivanek, L.J. Tirri, R.K. Margolis and R.U. Margolis (1976). In "Ganglioside Function: Biochemical and Pharmacological Implications: (ed. by G. Porcellati, B. Ceccarelli, and G. Tettamanti). Plenum Press, N.Y., p. 83.